Daiichi Sankyo Company (4568) WCLC/ESMO 2024 Conference summary

Conference overview

• The event highlighted recent data from WCLC and ESMO, focusing on progress in the DXd ADC portfolio and emerging next-generation ADCs.

• Presentations covered updates in lung, ovarian, endometrial, and breast cancers, as well as new biomarker strategies and early-stage assets.

• Key speakers included heads of global R&D and oncology clinical development, with Q&A sessions addressing regulatory, biomarker, and pipeline questions.

Key presentations and study updates

• Multiple oral presentations at WCLC 2024 highlighted new data from pivotal lung cancer trials, including TROPION-Lung01, DESTINY-Lung03, NeoCOAST-2, and IDeate-Lung01.

• TROPION-Lung01 final analysis showed datopotamab deruxtecan (Dato-DXd) improved PFS over docetaxel in previously treated NSCLC, with a manageable safety profile and a trend toward improved OS, especially in nonsquamous subgroups.

• DESTINY-Lung03 reported that trastuzumab deruxtecan (T-DXd) monotherapy achieved a 44.4% ORR and median PFS of 8.2 months in pretreated HER2-overexpressing NSCLC, with higher response rates in IHC 3+ and prior EGFR TKI subgroups.

• NeoCOAST-2 demonstrated that perioperative Dato-DXd plus durvalumab and chemotherapy led to the highest pCR (34.1%) and mPR (65.9%) rates among tested regimens in resectable NSCLC, with all arms showing manageable safety and high surgical feasibility.

• IDeate-Lung01 interim analysis showed ifinatamab deruxtecan (I-DXd) had a higher ORR at 12 mg/kg (54.8%) versus 8 mg/kg (26.1%) in extensive-stage SCLC, with rapid and durable responses and a tolerable safety profile.

Clinical trial highlights

• TROPION-Lung01 phase III showed significant PFS benefit for Dato-DXd in non-squamous NSCLC, though OS did not reach statistical significance; benefit was most pronounced in non-squamous subgroups.

• A novel TROP2 biomarker (QCS-NMR) demonstrated potential to predict Dato-DXd efficacy, with higher prevalence and benefit in non-squamous patients; ongoing validation in pivotal trials.

• Dato-DXd monotherapy in ovarian and endometrial cancers showed encouraging response rates and manageable safety in heavily pretreated populations.

• HER3-DXd demonstrated meaningful activity and manageable safety in heavily pretreated HR+/HER2- breast cancer, with efficacy independent of HER2/HER3 expression.

• DS-9606, a CLDN6-directed ADC with a PBD payload, showed early signs of efficacy and a manageable safety profile in a phase I trial, especially in germ cell tumors.